Search Results (24)

The potential of RNA-based liquid biopsy is increasingly being recognized in diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin’s lymphoma. This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n = 171) derived from a DLBCL PDTX model, including 27 humanized (HIS) PDTX, 8 HIS non-PDTX, and 21 non-HIS PDTX non-obese diabetic (NOD)-scid IL2Rgnull (NSG) mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), CD20-targeted human IFNα2-based AcTaferon combined with CHOP (huCD20-Fc-AFN-CHOP), or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform. RNA sequencing data of the formalin-fixed paraffin-embedded (FFPE) tissue and blood plasma samples of the original patient were included. Flow cytometry was performed on immune cells isolated from whole blood, spleen, and bone marrow. Bulk deconvolution was performed using the Tabula Sapiens v1 basis matrix. Both R-CHOP and huCD20-Fc-AFN-CHOP were able to control tumor growth in most mice. Xenograft tumor volume was strongly associated with circulating tumor RNA (ctRNA) concentration (p < 0.001, R = 0.89), as well as with the number of detected human genes (p < 0.001, R = 0.79). Abundance analysis identified tumor-specific biomarkers that were dynamically tracked during tumor growth or treatment. An 8-gene signature demonstrated high accuracy for assessing therapy response (AUC 0.92). The tumoral gene detectability in the ctRNA of the PDTX-derived plasma was associated with RNA abundance levels in the patient’s tumor tissue and blood plasma (p < 0.001), confirming that tumoral gene abundance contributes to the cell-free RNA (cfRNA) profile. Decomposing the transcriptome, however, revealed high inter- and intra-mouse variability, which was lower in the HIS PDTX mice, indicating an impact of human engraftment on the stability and profile of cfRNA. Immunochemotherapy resulted in B cell depletion, and tumor clearance was reflected by a decrease in the fraction of human CD45+ cells. Lastly, bulk deconvolution provided complementary biological insights into the composition of the tumor and circulating immune system. In conclusion, the blood plasma-derived transcriptome serves as a biomarker source in a preclinical PDTX model, enables the assessment of biological pathways, and enhances the understanding of cfRNA dynamics. Full article

Objective: To compare perceived parental style in a large cohort of adults with congenital heart disease (ACHD) to healthy reference (RCs). Furthermore, factors associated with perceived parental style were determined in ACHD. Patients and Methods: From September 2016 to April 2019, 912 ACHD (34.9 ± 10.4 years, 45% female) and 175 RCs (35.8 ± 12.2 years, 53% female) completed the Measure of Parental Style (MOPS) questionnaire. Results: After adjusting for age and sex, ACHD recalled the parental style of both their parents to be significantly less indifferent (mother: ACHD: 1.2 ± 0.01 vs. RC: 1.3 ± 0.03, p < 0.001; father: ACHD: 1.3 ± 0.02 vs. RC: 1.7 ± 0.05, p < 0.001), overcontrolling (mother: ACHD: 1.6 ± 0.63 vs. RC: 1.9 ± 0.62, p < 0.001; father: ACHD: 1.4 ± 0.52 vs. RC: 1.5 ± 0.50, p < 0.001), and abusive (mother: ACHD: 1.2 ± 0.47 vs. RC: 1.4 ± 0.46, p < 0.001; father: ACHD: 1.3 ± 0.59 vs. RC: 1.5 ± 0.57, p < 0.001) than healthy controls did. In ACHD, female sex (β = 0.068, p = 0.017), higher age (β = 0.005, p = 0.003), Ebstein anomaly (β = 0.170, p = 0.005), and cyanotic CHD (β = 0.336, p = 0.004) contribute to perceiving the parental style of at least one of the parents negatively. Conclusions: While ACHD appear to recall the parental style to be less negative, subgroup analysis revealed specific patients at risk. These findings point to the need for interventions in specific subgroups susceptible to psychological distress. Full article

A statistical analysis was applied to Northern Hemisphere land surface temperatures (1850–2018) to try to identify the main drivers of the observed warming since the mid-19th century. Two different temperature estimates were considered—a rural and urban blend (that matches almost exactly with most current estimates) and a rural-only estimate. The rural and urban blend indicates a long-term warming of 0.89 °C/century since 1850, while the rural-only indicates 0.55 °C/century. This contradicts a common assumption that current thermometer-based global temperature indices are relatively unaffected by urban warming biases. Three main climatic drivers were considered, following the approaches adopted by the Intergovernmental Panel on Climate Change (IPCC)’s recent 6th Assessment Report (AR6): two natural forcings (solar and volcanic) and the composite “all anthropogenic forcings combined” time series recommended by IPCC AR6. The volcanic time series was that recommended by IPCC AR6. Two alternative solar forcing datasets were contrasted. One was the Total Solar Irradiance (TSI) time series that was recommended by IPCC AR6. The other TSI time series was apparently overlooked by IPCC AR6. It was found that altering the temperature estimate and/or the choice of solar forcing dataset resulted in very different conclusions as to the primary drivers of the observed warming. Our analysis focused on the Northern Hemispheric land component of global surface temperatures since this is the most data-rich component. It reveals that important challenges remain for the broader detection and attribution problem of global warming: (1) urbanization bias remains a substantial problem for the global land temperature data; (2) it is still unclear which (if any) of the many TSI time series in the literature are accurate estimates of past TSI; (3) the scientific community is not yet in a position to confidently establish whether the warming since 1850 is mostly human-caused, mostly natural, or some combination. Suggestions for how these scientific challenges might be resolved are offered. Full article

Background: Diaphragm eventration (DE) represents a frequent problem with consecutive major impacts on respiratory function and the quality of life of the patients. The role of diaphragmatic plication (DP) is still underestimated. The aim of the present study is to evaluate the efficacy of minimally-invasive surgical diaphragmatic plication for the management of unilateral diaphragmatic eventration, to the best of our knowledge, this is the largest series reported in the literature using a non-resectional technique. Methods: All patients with unilateral diaphragmatic paralysis admitted for diaphragmatic plication (DP) between January 2008 and December 2022 formed the cohort of this retrospective analysis. DP procedure was done to plicate the diaphragm without resection or replacement with synthetic materials. Patients were divided into two groups: Group I included patients who underwent DP through an open thoracotomy, and Group II included patients who underwent DP through video-assisted thoracoscopic surgery (VATS). Data from all patients were collected prospectively and subsequently analyzed retrospectively. Patients’ characteristics, lung function tests, radiological findings, type of surgical procedures, complications, and postoperative follow-up were compared. The primary outcome measure was the postoperative result (deeper position of the paralyzed diaphragm) and improvement of dyspnea. The secondary outcome was lung function values over a long-term follow-up. Results: The study included a total of 134 patients who underwent diaphragmatic plication during the study period. 94 (71.7%) were males, mean age of 64 (SD ± 14.0). Group I (thoracotomy group) consisted of 46 patients (35 male). Group II (VATS-group) consisted of 88 patients (69 male). The majority of patients demonstrated impaired lung functions (n = 126). The mean length of diaphragmatic displacement was 8 cm (SD ± 113.8 cm). The mean duration of the entire procedure, including placement of the epidural catheter (EDC), was longer in group I than in group II (p = 0.016). This was also observed for the mean length of the surgical procedure itself (p = 0.031). Most patients in group I had EDC (n = 38) (p = 0.001). Patients in group I required more medication for pain control (p = 0.022). A lower position of the diaphragm was achieved in all patients (p < 0.001). The length of hospital stay was 7 (SD ± 4.5) days in group I vs. 4.5 (SD ± 3.2) days in group II (p = 0.036). Minor complications occurred in 3% (n = 4) in group I vs. 2% (n = 3) in group II. No mortality was observed in any of the groups. Postoperative follow-up of patients at 6, 12, and 24 months showed a significant increase in forced vital capacity (FVC) up to 25% (SD ± 10%–35%) (p = 0.019), in forced expiratory volume in 1 s (FEV1) up to 20% (SD ± 12%–38%) in both groups (p = 0.026), also in the diffusion capacity of carbon monoxide (DLCO) up to 15% (SD ± 10%–20%) was noticed in both groups. Chronic pain symptoms were noted in 13% (n = 6) in group I vs. 2% (n = 2) in group II (p = 0.014). Except for one patient in group II, no recurrence of DE was observed. Conclusions: Diaphragm plication is an effective procedure to reduce debilitating dyspnea and improve lung function in patients suffering from diaphragm eventration. Minimally invasive diaphragmatic plication using VATS procedures is a safe and feasible procedure for the management of unilateral diaphragmatic paralysis. VATS-DP is superior to open procedure in terms of pain management and length of hospital stay, hence, accelerated recovery is more likely. Careful patient selection is crucial to achieving optimal outcomes. Prospective studies are needed to validate these results. Full article

Stroke patients show some degree of spontaneous functional recovery, but this is not sufficient to prevent long-term disability. One promising approach is to characterize the dynamics of stroke recovery genes in the lesion and distant areas. We induced sensorimotor cortex lesions in adult C57BL/6J mice using photothrombosis and performed qPCR on selected brain areas at 14, 28, and 56 days post-stroke (P14-56). Based on the grid walk and rotating beam test, the mice were classified into two groups. The expression of cAMP pathway genes Adora2a, Pde10a, and Drd2, was higher in poor- compared to well-recovered mice in contralesional primary motor cortex (cl-MOp) at P14&56 and cl-thalamus (cl-TH), but lower in cl-striatum (cl-Str) at P14 and cl-primary somatosensory cortex (cl-SSp) at P28. Plasticity and axonal sprouting genes, Lingo1 and BDNF, were decreased in cl-MOp at P14 and cl-Str at P28 and increased in cl-SSp at P28 and cl-Str at P14, respectively. In the cl-TH, Lingo1 was increased, and BDNF decreased at P14. Atrx, also involved in axonal sprouting, was only increased in poor-recovered mice in cl-MOp at P28. The results underline the gene expression dynamics and spatial variability and challenge existing theories of restricted neural plasticity. Full article

Background: Our aim is to assess the utility and associations of quantitative bone marrow attenuation (BMA) values measured on clinical dual-energy computed tomography (DECT) exams in non-hematooncologic subjects with skeletal regions, patient age, gender, and other clinical variables. Methods: Our local ethics committee approved this retrospective image data analysis. Between July 2019 and July 2021, 332 eligible patients (mean age, 64 ± 18 years; female, 135) were identified. Inclusion criteria were the availability of a standardized abdominopelvic DECT data set acquired on the same scanner with identical protocol. Eleven regions-of-interest were placed in the T11-L5 vertebral bodies, dorsal iliac crests, and femur necks. Patient age, gender, weight, clinical, habitual variables, inflammation markers, and anemia were documented in all cases. Results: Multi-regression analyses (all, p < 0.05) identified age as the strongest predictor of lumbar BMA (standardized coefficient: β = −0.74), followed by CRP (β = 0.11), LDH (β = 0.11), and gender (β = −0.10). In the lower thoracic spine, age was the strongest predictor (β = −0.58) of BMA, followed by gender (β = −0.09) and LDH (β = 0.12). In femoral bones, age was negatively predictive of BMA (β = −0.12), whereas LDH and anemia were positively predictive (β = 0.16 both). Heart insufficiency significantly decreased (β = 0.12, p = 0.034) a BMA value gradient from higher to lower HU values along the vertebrae T11 and L5, whereas age significantly increased this gradient (β = −0.2, p ≤ 0.001). Conclusions: DECT-based BMA measurements can be obtained from clinical CT exams. BMA values are negatively associated with patient age and influenced by gender, anemia, and inflammatory markers. Full article

Our aim was to compare the image quality and patient dose of contrast-enhanced oncologic chest-CT of a first-generation photon-counting detector (PCD-CT) and a second-generation dual-source dual-energy CT (DSCT). For this reason, one hundred consecutive oncologic patients (63 male, 65 ± 11 years, BMI: 16–42 kg/m²) were prospectively enrolled and evaluated. Clinically indicated contrast-enhanced chest-CT were obtained with PCD-CT and compared to previously obtained chest-DSCT in the same individuals. The median time interval between the scans was three months. The same contrast media protocol was used for both scans. PCD-CT was performed in QuantumPlus mode (obtaining full spectral information) at 120 kVp. DSCT was performed using 100 kV for Tube A and 140 kV for Tube B. “T3D” PCD-CT images were evaluated, which emulate conventional 120 keV polychromatic images. For DSCT, the convolution algorithm was set at I31f with class 1 iterative reconstruction, whereas comparable Br40 kernel and iterative reconstruction strengths (Q1 and Q3) were applied for PCD-CT. Two radiologists assessed image quality using a five-point Likert scale and performed measurements of vessels and lung parenchyma for signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and in the case of pulmonary metastases tumor-to-lung parenchyma contrast ratio. PCD-CT CNR_vessel was significantly higher than DSCT CNR_vessel (all, p < 0.05). Readers rated image contrast of mediastinum, vessels, and lung parenchyma significantly higher in PCD-CT than DSCT images (p < 0.001). Q3 PCD-CT CNR_{lung_parenchyma} was significantly higher than DSCT CNR_{lung_parenchyma} and Q1 PCD-CT CNR_{lung_parenchyma} (p < 0.01). The tumor-to-lung parenchyma contrast ratio was significantly higher on PCD-CT than DSCT images (0.08 ± 0.04 vs. 0.03 ± 0.02, p < 0.001). CTDI, DLP, SSDE mean values for PCD-CT and DSCT were 4.17 ± 1.29 mGy vs. 7.21 ± 0.49 mGy, 151.01 ± 48.56 mGy * cm vs. 288.64 ± 31.17 mGy * cm and 4.23 ± 0.97 vs. 7.48 ± 1.09, respectively. PCD-CT enables oncologic chest-CT with a significantly reduced dose while maintaining image quality similar to a second-generation DSCT for comparable protocol settings. Full article

Background: Modern personalised medicine requires patient-tailored decisions. This is particularly important when considering pharmacological cardioversion for the acute treatment of haemodynamically stable atrial fibrillation and atrial flutter in a shared decision-making process. We aimed to develop and validate a predictive model to estimate the individual probability of successful pharmacological cardioversion using different intravenous antiarrhythmic agents. Methods: We analysed data from a prospective atrial fibrillation registry comprising 3053 cases of first-detected or recurrent haemodynamically stable, non-permanent, symptomatic atrial fibrillation presenting to an Austrian academic emergency department between January 2012 and December 2017. Using multivariable analysis, a prediction score was developed and externally validated. The clinical utility of the score was assessed using decision curve analysis. Results: A total of 1528 cases were included in the development cohort (median age 69 years, IQR 58–76; 43.9% female), and 1525 cases were included in the validation cohort (median age 68 years, IQR (58–75); 39.5% female). Finally, 421 cases were available for score development and 330 cases for score validation The weighted score included atrial flutter (8 points), duration of symptoms associated with AF (<24 h; 8 points), absence of previous electrical cardioversion (10 points), and the specific intravenous antiarrhythmic drug (amiodarone 10 points, vernakalant 11 points, ibutilide 13 points). The final score, the “Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) score,” showed good calibration (R² = 0.955 and R² = 0.954) and discrimination in both sets (c-indices: 0.68 and 0.66) and net clinical benefit. Conclusions: A predictive model was developed to estimate the success of intravenous pharmacological cardioversion using different antiarrhythmic agents in a cohort of patients with haemodynamically stable, non-permanent, symptomatic atrial fibrillation. External temporal validation confirmed good calibration, discrimination, and clinical usefulness. The SIC-AF score may help patients and physicians jointly decide on the appropriate treatment strategy for acute symptomatic atrial fibrillation. Registration: NCT03272620. Full article

Introduction: Childhood cancer survivors (CCS) might be at high risk of additional chronic diseases due to cardiotoxic side effects. The aim of this study was to analyze long-term side effects of cancer therapy on vascular structure/function, cardiac biomarkers and on physical activity. Methods: In total, 68 asymptomatic patients aged 16–30 years with childhood cancer (diagnosed 10.6 ± 3.9 years ago) were examined from 2015–2020. (Central) blood pressure and pulse wave velocity were registered via the oscillometric method, while carotid intima-media thickness (cIMT) was measured non-invasively by ultrasound. cIMT values of patients were compared to healthy controls (n = 68; aged 22.3 ± 3.5 years). Patients’ exercise capacity was recorded. The plasma N-terminal pro-brain natriuretic protein (NTproBNP) and troponin levels were measured as cardiac biomarkers. CCS were categorized in groups with low, moderate and high anthracyclines. Results: No differences were found in cIMT between patients and controls as well as between patients with various anthracycline dosage. Patients with high dose anthracyclines showed a significant lower performance versus patients with moderate dose anthracyclines (84.4% of predicted VO₂peak; p = 0.017). A total of 11.6% of CCS had abnormal NTproBNP values which correlated with received anthracycline dosage (p = 0.024; r = 0.343). Conclusion: NTproBNP levels and exercise capacity might be early markers for cardiovascular dysfunction in CCS and should be included in a follow-up protocol, while cIMT and troponin seem not to be adequate parameters. Full article

The life expectancy of patients with Tetralogy of Fallot (ToF) has increased in recent years. As a result, other risk factors with later onset in life are in the focus of patient care. Endothelial function is an early indicator of cardiovascular risk and was investigated along further structural vessel properties. A total of 17 patients (41.7 ± 7.1 years, 8 women) with Tetralogy of Fallot were 1:2 matched for sex with 34 (38.9 ± 8.1 years, 16 women) healthy volunteers. Participants received an assessment of their endothelial function and a structural assessment of the aorta. Patients with ToF showed a reduced endothelial function determined by reactive hyperaemia index after adjusting for age, weight and height (ToF: 1.55 ± 0.31 vs. controls: 1.84 ± 0.47; p = 0.023). No differences in carotid intima-media thickness (cIMT) between the ToF and healthy controls (ToF: 0.542 ± 0.063 mm vs. controls: 0.521 ± 0.164 mm; p = 0.319) were found. Patients with ToF had reduced vascular function compared to healthy subjects. As the structural component is not affected, endothelial dysfunction seems not to have yet manifested itself as a morphological change. Nevertheless, long-term management of these patients should include vascular parameters. Full article

The assessment of aortic root dimensions is a cornerstone in cardiac pre-participation screening as dilation can result in severe cardiac events. Moreover, it can be a hint for an underlying connective tissue disease, which needs individualized sports counseling. This study examines the prevalence of aortic root dilatation in a cohort and its relationship to arterial stiffness as an early marker of cardiovascular risk due to vascular aging. From May 2012 to March 2018, we examined 281 young male athletes (14.7 ± 2.1 years) for their aortic root dimension. Moreover, we noninvasively assessed arterial stiffness parameter during pre-participation screening. Mean aortic diameter was 25.9 ± 3.1 mm and 18 of the 281 (6.4%) athletes had aortic root dilation without other clinical evidence of connective tissue disease. After adjusting for BSA, there was no association of aortic root diameter to pulse wave velocity (p = −0.054 r = 0.368) nor to central blood pressure (p = −0.029 r = 0.634). Thus, although a significant proportion of young athletes had aortic root dilatation, which certainly needs regular follow up, no correlation with arterial stiffness was found. It could be suggested that a dilated aortic root in young athletes does not alter pulse waveform and pulse reflection, and thus there is no increased cardiovascular risk in those subjects. Full article

Background: Overweight and obesity have become a major public health concern in recent decades, particularly in patients with chronic health conditions like congenital heart disease (CHD). This systematic review elaborates on the prevalence and the longitudinal development of overweight and obesity in children and adults with CHD. Methods: A systematic literature search was conducted in PubMed, Cochrane, and Scopus from January 2010 to December 2020 on overweight and obesity prevalence in children and adults with CHD. Results: Of 30 included studies, 15 studies evaluated 5680 pediatric patients with CHD, 9 studies evaluated 6657 adults with CHD (ACHD) and 6 studies examined 9273 both pediatric patients and ACHD. Fifteen studies received the quality rating “good”, nine studies “fair”, and six studies “poor”. In children with CHD, overweight prevalence was between 9.5–31.5%, and obesity prevalence was between 9.5–26%; in ACHD, overweight prevalence was between 22–53%, and obesity was between 7–26%. The prevalence of overweight and obesity was thereby similar to the general population. Overweight and obesity have been shown to increase with age. Conclusion: The prevalence of overweight and obesity in children and adults with CHD is similar to the general population, demonstrating that the growing obesity pandemic is also affecting the CHD population. Full article

Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors. Full article

Background: The association between physical activity (PA) and arterial stiffness is particularly important in children with congenital heart disease (CHD) who are at risk for arterial stiffening. The aim of this study was to examine the association between objectively measured PA and arterial stiffness in children and adolescents with CHD. Methods: In 387 children and adolescents with various CHD (12.2 ± 3.3 years; 162 girls) moderate-to-vigorous PA (MVPA) was assessed with the “Garmin vivofit jr.” for 7 consecutive days. Arterial stiffness parameters including pulse wave velocity (PWV) and central systolic blood pressure (cSBP) were non-invasively assessed by oscillometric measurement via Mobil-O-Graph^®. Results: MVPA was not associated with PWV (ß = −0.025, p = 0.446) and cSBP (ß = −0.020, p = 0.552) in children with CHD after adjusting for age, sex, BMI z-score, peripheral systolic blood pressure, heart rate and hypertensive agents. Children with CHD were remarkably active with 80% of the study population reaching the WHO recommendation of average 60 min of MVPA per day. Arterial stiffness did not differ between low-active and high-active CHD group after adjusting for age, sex, BMI z-score, peripheral systolic blood pressure, heart rate and hypertensive agents (PWV: F = 0.530, p = 0.467; cSBP: F = 0.843, p = 0.359). Conclusion: In this active cohort, no association between PA and arterial stiffness was found. Longer exposure to the respective risk factors of physical inactivity might be necessary to determine an impact of PA on the vascular system. Full article

The performance of artificial nerve guidance conduits (NGC) in peripheral nerve regeneration can be improved by providing structures with multiple small channels instead of a single wide lumen. 3D-printing is a strategy to access such multi-channeled structures in a defined and reproducible way. This study explores extrusion-based 3D-printing of two-component hydrogels from a single cartridge printhead into multi-channeled structures under aseptic conditions. The gels are based on a platform of synthetic, anhydride-containing oligomers for cross-linking of gelatinous peptides. Stable constructs with continuous small channels and a variety of footprints and sizes were successfully generated from formulations containing either an organic or inorganic gelation base. The adjustability of the system was investigated by varying the cross-linking oligomer and substituting the gelation bases controlling the cross-linking kinetics. Formulations with organic N‑methyl-piperidin-3-ol and inorganic K₂HPO₄ yielded hydrogels with comparable properties after manual processing and extrusion-based 3D-printing. The slower reaction kinetics of formulations with K₂HPO₄ can be beneficial for extending the time frame for printing. The two-component hydrogels displayed both slow hydrolytic and activity-dependent enzymatic degradability. Together with satisfying in vitro cell proliferation data, these results indicate the suitability of our cross-linked hydrogels as multi-channeled NGC for enhanced peripheral nerve regeneration. Full article